Organic anion-transporting polypeptides (OATPs/SLCOs)

摘要: Species differences exist in OATP transporters, such that human hepatic OATPs are not orthologs to preclinical species e.g. the mouse, rat and dog. The contributions uptake should be carefully considered when quantitatively predicting extent of inhibitory effects humans from animal data. OATP1B1 1B3 selectively expressed on sinusoidal membranes hepatocytes liver, often selected as specific carriers for drugs targeted at liver. most relevant transporters determine rate elimination by hepatobiliary excretion and/or cytochrome P450 (CYP) metabolism. Inhibition OATP-mediated transport can cause clinical significant DDIs. Regulatory agencies, including FDA EMA, require drug interactions assessed all candidates significantly eliminated via also involved drug-food GI absorption sites, although magnitude is smaller than systemic vitro may stimulated an inhibitor stimulation appears substrate dependent. This taken into consideration selecting probe substrates evaluation potential